The purpose of this project is to understand the regulation of mouse natural killer (NK) cell activity and proliferation in vivo. By the techniques of centrifugal elutriation and a newly developed single cell cytotoxicity assay which detects lysis mediated by blast NK cells, we have shown that virus infections and purified interferon (IFN) stimulate the blastogenesis of NK cells. We propose to further characterize this system by studying the kinetics of blastogenesis, the organ distribution of blast cells and the regulation of blastogenesis in different strains of mice. Lymphocytic choriomeningitis virus, poly I:C and purified IFN-beta will be used as inducers. Experiments are designed to examine the precursor and fate of the blast NK cell and to determine the mechanism by which IFN acts to cause blastogenesis. An analysis of the blast NK cell response will be made during T-cell-dependent immune reactions and under conditions of interleukin-2 or IFN-gamma treatment. The effects of tumor growth on the blastogenesis of NK cells will be tested, and attempts will be made to localize blast NK cells associated with tumors. Understanding the mechanisms by which NK cell activity and proliferation can be regulated is important because these cells are considered responsible for tumor surveillance in vivo.